THE COOH-TERMINAL REGION OF PRB2 P130 BINDS TO HISTONE-DEACETYLASE-1 (HDAC1), ENHANCING TRANSCRIPTIONAL REPRESSION OF THE E2F-DEPENDENT CYCLIN-A PROMOTER/

The tumor suppressor retinoblastoma protein family members pRb, p107, and pRb2/p130 are potent negative transcriptional regulators. The best understood target is the transcription factor E2F, which activates ce ll cycle-dependent transcription of genes controlling and promoting th e cell division cycle (e,g,, cyclin A). pRb2/p130 is known to be impor tant in implementing cell cycle exit into G(0) due to serum deprivatio n or various differentiation programs. Several recent studies demonstr ated the effect histone acetylases and histone deacetylases (HDACs) ha ve on fine-tuning transcriptional regulation of eucaryotic cells. In t his study, we demonstrate that pRb2/p130 binds to HDAC1, This interact ion increases the ability of pRb2/p130 to inhibit transcription of the E2F-dependent cyclin A promoter in vivo. We also identify the COOH-te rminal 35aa as being necessary for stable interaction between HDAC1 an d pRb2/p130.